This application proposes to renew the Medical Scientist Training Program (MSTP) at Stanford. Since its inception forty years ago, the program has graduated 222 individuals, many of whom have become national leaders in academic medicine and biomedical research. The program provides a rich environment and unparalleled opportunities for developing a career dedicated to scientific investigation, in which individualization of curricular and research plans tailored to each trainee is a hallmark. A unique aspect of the program is the environment provided by a true University, with Schools of Medicine, Engineering, and Humanities &Sciences located on a single campus that facilitates and encourages interaction between scientists from different disciplines. An important component of this environment with special relevance to the MSTP is the Bio-X program for Biomedical Engineering and Interdisciplinary Sciences. Designed to bridge the life, physical, and mathematical sciences to address current challenges in medicine and biology with new ways of thinking, the Bio-X program has drawn an increasing proportion of MSTP applicants with undergraduate training and expertise in the physical sciences and engineering. A second unique aspect of the program is "internal admissions", whereby 10-15% of the trainees enter at years 3, 4, or 5, having initiated their training as traditional Stanford medical students, then choosing to pursue a research-oriented career as a result of the Scholarly Concentration Program for medical students. Medical school at Stanford is also unique, with major clinical training centers in tertiary care, county hospital, and HMO settings that provide opportunities for students to learn both about different types of patient care and how best to care for their patients. As a result of the Scholarly Concentration Program, most Stanford students spend an extra year pursuing interests in laboratory research, public health, or community service;thus, MSTP students are surrounded by colleagues whose interests go beyond a traditional curriculum. Important changes to the Stanford MSTP in the last funding cycle include a series of new programs for academic enrichment and career counseling, and an expanded institutional and research mentor commitment that has increased the proportion of highly qualified applicants that are offered admission;the number of fully supported MSTP students is now more than twice the number of trainee positions provided by the NIGMS T32. We propose to continue this trend of innovation and interdisciplinary training, in which training grant resources are leveraged, and 10-12 individuals are admitted per year for a program length of 7- 8 years. RELEVANCE: Continued improvement in human health depends on translation of fundamental knowledge to clinical settings, and integration of approaches from several different disciplines. The Stanford MSTP embraces and promotes these goals, training physician-scientists to be academic leaders for future advances in biomedical research.